p63 induces CD4+ T-cell chemoattractant TARC/CCL17 in human epithelial cells.
To preserve immunosurveillance, epithelial cells support T-cell trafficking toward inflammatory foci. However, how epithelial cells are enrolled in recruiting T cells has not been fully elucidated. In this study we investigated the function of p63, a p53 family member, in the regulation of the expression of various types of chemokine ligands by focusing on the property of p63 as an epitheliotropic transcription factor. As assessed by experiments using three different human epithelial cell lines with small-interfering RNAs or plasmids of p63, certain CC chemokine ligands were found to be under the control of p63. In these CC chemokine ligands, p63 had the common capacity to upregulate TARC/CCL17 in the different cell lines, whose receptor CCR4 was preferentially presented on CD4(+) T cells such as memory, regulatory, IL-17-producing and type II helper T cells. More interestingly, when cells were stimulated with transforming growth factor-beta (TGF-beta) or epidermal growth factor (EGF) as observed during tissue repair process, the expression of p63 and TARC/CCL17 was concomitantly suppressed. This implies that, in local inflammatory regions with general epithelial tissue remodeling, the p63-TARC/CCL17 axis may participate in the engagement of efficient immune reactions by specified T-cell subsets.
Kubo
Terufumi
T
Department of Pathology, Sapporo Medical University School of Medicine, Sapporo, Japan.
Ichimiya
Shingo
S
Tonooka
Akiko
A
Nagashima
Tsutomu
T
Kikuchi
Tomoki
T
Sato
Noriyuki
N
D015496:CD4-Positive T-Lymphocytes / Q000276:immunology* / Q000378:metabolism; D002460:Cell Line; D054414:Chemokine CCL17 / Q000276:immunology / Q000378:metabolism*; D004815:Epidermal Growth Factor / Q000276:immunology / Q000378:metabolism; D004847:Epithelial Cells / Q000166:cytology / Q000276:immunology* / Q000378:metabolism; D006801:Humans; D008565:Membrane Proteins / Q000276:immunology / Q000378:metabolism*; D054387:Receptors, CXCR / Q000276:immunology / Q000378:metabolism*; D014158:Transcription, Genetic; D016212:Transforming Growth Factor beta / Q000276:immunology / Q000378:metabolism
C106230:CCL17 protein, human; C081876:CKAP4 protein, human; D054414:Chemokine CCL17; D008565:Membrane Proteins; D054387:Receptors, CXCR; D016212:Transforming Growth Factor beta; D004815:Epidermal Growth Factor